Multiple sclerosis (MS) is characterized clinically by episodes of relapsing or chronic paralysis and the pathogenesis is attributed to T-cell-mediated inflammation of the CNS. Clinical, histopathological and immunological similarities between MS and experimental autoimmune encephalomyelitis (EAE) allow EAE to be used as a model for therapeutic approaches to MS. Inhibition of murine relapsing EAE with multiple oral administrations of myelin basic protein (MBP) to BP10.PL mice has been reported recently. Two mechanisms have been proposed for MBP-induced oral tolerance - active suppression and clonal anergy/deletion. Deciphering mechanisms of oral tolerance to MBP and testing tolerizing strategies for protection from EAE have been facilitated by the development of MBP T-cell receptor (TCR) transgenic (Tg) mice. These mice express a TCR specific for the immunodominant MBP epitope (NAc 1-11) on 95% of their CD4+ T-cells and are highly susceptible to EAE. The investigator has preliminary data showing that orally administered MBP not only protects MBP TCR Tg mice from EAE but also induces a profound reduction of Tg+ cells from the periphery. This is followed by the return of a Tg population with decreased functional capacity. This evidence supports the investigator's hypothesis that high dose oral administration of an autoantigen induces early deletion of antigen-reactive cells, followed by a return to the periphery of autoantigen-reactive cells rendered anergic. The investigator proposes to address several questions pertaining to the mechanism and ideal conditions for MBP-induced oral tolerance. The investigator will differentiate between immediate trafficking or deletion of MBP-specific Tg cells after MBP feeding. She will characterize the duration of MBP-induced oral tolerance. She will optimize conditions for oral tolerance to MBP. Therefore, at their conclusion these studies will have 1) defined the effects of feeding antigen on antigen-specific T-cells and 2) optimized oral tolerance for application to a chronic inflammatory disease.